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Development and Characterization of a Probe Device toward Intracranial Spectroscopy of Traumatic Brain Injury.
No full textTraumatic brain injury is a leading cause of mortality worldwide, often affecting individuals at their most economically active yet no primary disease-modifying interventions exist for their treatment. Real-time direct spectroscopic examination of the brain tissue within the context of traumatic brain injury has the potential to improve the understanding of injury heterogeneity and subtypes, better target management strategies and organ penetrance of pharmacological agents, identify novel targets for intervention, and allow a clearer understanding of fundamental biochemistry evolution. Here, a novel device is designed and engineered, delivering Raman spectroscopy-based measurements from the brain through clinically established cranial access techniques. Device prototyping is undertaken within the constraints imposed by the acquisition and site dimensions (standard intracranial access holes, probe's dimensions), and an artificial skull anatomical model with cortical impact is developed. The device shows a good agreement with the data acquired a standard commercial Raman, and the spectra measured are comparable in terms of quality and detectable bands to the established traumatic brain injury model. The developed proof-of-concept device demonstrates the feasibility for real-time optical brain spectroscopic interface while removing the noise of extracranial tissue and with further optimization and validation, such technology will be directly translatable for integration into currently available standards of neurological care
Factors associated with electrical stimulation-induced performance fatigability are dependent upon stimulation location.
No full textNEW FINDINGS
What is the central question of this study? How does peripheral nerve stimulation (PNS) compare with neuromuscular electrical stimulation (NMES) used clinically to reduce muscle atrophy? What is the main finding and its importance? NMES resulted in progressive increases in M-wave duration and delay of muscle relaxation throughout a single stimulation protocol, findings not observed with PNS. This suggests PNS recruits from a wider pool of muscle fibres/motor units, providing a more favourable alternative to NMES for rehabilitation intervention.
ABSTRACT
Neuromuscular electrical stimulation (NMES) is increasingly viewed as a central tenet to minimise muscle loss during periods of disuse/illness - typically applied directly over a muscle belly. Peripheral nerve stimulation (PNS) is afforded less attention, despite providing a more global contractile stimulus to muscles. We investigated NMES versus PNS in relation to performance fatigability and peripheral contributions to voluntary force capacity. Two fatigue protocols were assessed separately: (1) over-quadriceps NMES and (2) peripheral (femoral) nerve stimulation (PNS). Before and after each session, a maximal voluntary contraction (MVC) was performed to assess force loss. Knee-extensor force was measured throughout to assess contractile function in response to submaximal electrical stimulation, and M-wave features quantified myoelectrical activity. NMES and PNS induced similar voluntary (MVC, NMES: -12 ± 9%, PNS: -10 ± 8%, both P < 0.001) and stimulated (NMES: -45 ± 12%, PNS -27 ± 27%, both P < 0.001) force reductions. Although distinct between protocols, myoelectrical indicators of muscle recruitment (M-wave area and amplitude) and nerve conduction time did not change throughout either protocol. Myoelectrical propagation speed, represented as M-wave duration, and the delay before muscle relaxation began both progressively increased during NMES only (P < 0.05 and P < 0.001, respectively). NMES myoelectrical changes suggested performance fatigability, indicating activation of superficial fibres only, which was not observed with PNS. This suggests PNS recruits a wider pool of muscle fibres and motor units and is a favourable alternative for rehabilitation. Future work should focus on implementing PNS interventions in clinically relevant scenarios such as immobilisation, care homes and critical illness
Effect of COVID-19 on the clinical course of diabetic ketoacidosis (DKA) in people with type 1 and type 2 diabetes.
No full textOBJECTIVE
COVID-19 in people with diabetes is associated with a disproportionately worse prognosis. DKA is an acute complication of diabetes with a mortality rate of approximately 0.67%. Little is known about the natural history of DKA in the presence of COVID-19. This study aimed to explore the effects of COVID-19 on presentation, clinical course and outcome in patients presenting with DKA.
DESIGN
Retrospective cohort study.
METHODS
All patients treated for DKA between 1 March 2020 and 30 May 2020 were included. Patients were categorised as COVID-positive or COVID-negative based on swab test. A pre-COVID group was established using data from 01 March 2019 to 30 May 2019 as external control. Data regarding demographics, diabetes type, pH, bicarbonate, lactate, glucose, DKA duration, complications and outcome were collected.
RESULTS
A total of 88 DKA episodes were included in this study. There was no significant difference in the severity or duration of DKA between the three groups. COVID-positive T1DM were more hyperglycaemic on admission compared to COVID-negative and pre-COVID patients. There was an over representation of T2DM in COVID-positive patients with DKA than in pre-COVID or COVID-negative groups.
CONCLUSION
COVID-19 appears to influence the natural history of DKA differently in T1DM and T2DM. Patients with T1DM and COVID-19 presented with more hyperglycaemia (60mmol/l (35.9-60.0) vs. 31.4mmol/l (28.0-39.1) vs. 24mmol/l (20.2-33.75), respectively). Patients with T2DM were unusually presenting in DKA when infected with COVID-19 with greater ICU need and higher mortality rates. A collaborative, multi-centre study is needed to provide more definitive results
Validation of a combined ELISA to detect IgG, IgA and IgM antibody responses to SARS-CoV-2 in mild or moderate non-hospitalised patients.
No full textBACKGROUND
Frequently SARS-CoV-2 results in mild or moderate disease with potentially lower concentrations of antibodies compared to those that are hospitalised. Here, we validated an ELISA using SARS-CoV-2 trimeric spike glycoprotein, with targeted detection of IgG, IgA and IgM (IgGAM) using serum and dried blood spots (DBS) from adults with mild or moderate disease.
METHODS
Targeting the SARS-CoV-2 trimeric spike, a combined anti-IgG, IgA and IgM serology ELISA assay was developed using 62 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 624 COVID-19 negative samples. The assay was validated using 73 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 359 COVID-19 negative serum samples with an additional 81 DBSs. The assay was further validated in 226 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 426 COVID-19 negative clinical samples.
RESULTS
A sensitivity and specificity of 98.6% (95% CI, 92.6-100.0), 98.3% (95% CI, 96.4-99.4), respectively, was observed following validation of the SARS-CoV-2 ELISA. No cross-reactivities with endemic coronaviruses or other human viruses were observed, and no change in results were recorded for interfering substances. The assay was stable at temperature extremes and components were stable for 15 days once opened. A matrix comparison showed DBS to correlate with serum results. Clinical validation of the assay reported a sensitivity of 94.7% (95% CI, 90.9-97.2%) and a specificity of 98.4% (95% CI, 96.6-99.3%).
CONCLUSIONS
The human anti-IgGAM SARS-CoV-2 ELISA provides accurate and sensitive detection of SARS-CoV-2 antibodies in non-hospitalised adults with mild or moderate disease. The use of dried blood spots makes the assay accessible to the wider community
Stoma formation as a palliative procedure: the role of the clinical nurse specialist in maintaining quality of life.
No full textMore than half of patients diagnosed with colon cancer present at an advanced stage, and palliative treatment may involve stoma formation. A literature review was undertaken to determine the potential effects of stoma formation as a palliative procedure on a patient's quality of life, and to examine the role of the clinical nurse specialist in this situation. Limited literature was found on this specific subject, so established evidence surrounding stoma formation and quality of life was examined in relation to palliative care. The clinical nurse specialist provides expert knowledge that can help to limit stoma complications and is also able to conduct assessments that identify holistic concerns affecting quality of life. However, access to a clinical nurse specialist may be limited, particularly when surgery is performed as an emergency. There is the potential for research surrounding patient experiences that may improve service provision for this client group
Emerging therapies and their delivery for treating age-related macular degeneration.
No full textAge-related macular degeneration (AMD) is the most common cause of blindness in the Western world and is characterised in its latter stages by retinal cell death and neovascularisation and earlier stages with the loss of parainflammatory homeostasis. Patients with neovascular AMD (nAMD) are treated with frequent intraocular injections of anti-vascular endothelial growth factor (VEGF) therapies, which are not only unpopular with patients, but carry risks of sight-threatening complications. A minority of patients are unresponsive with no alternative treatment available and some patients who respond initially eventually develop a tolerance to treatment. New therapeutics with improved delivery methods and sustainability of clinical effects are required, in particular for non-neovascular AMD (90% of cases and no current approved treatments). There are age-related and disease-related changes that occur which can affect ocular drug delivery. Here, we review the latest emerging therapies for AMD, their delivery routes, and implications for translating to clinical practice
COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience.
No full textBACKGROUND
As of November 2020, severe acute respiratory syndrome coronavirus 2 has resulted in 55 million infections worldwide and more than 1.3 million deaths from coronavirus disease 2019 (COVID-19). Outcomes following severe acute respiratory syndrome coronavirus 2 infection in individuals with primary immunodeficiency (PID) or symptomatic secondary immunodeficiency (SID) remain uncertain.
OBJECTIVES
We sought to document the outcomes of individuals with PID or symptomatic SID following COVID-19 in the United Kingdom.
METHODS
At the start of the COVID-19 pandemic, the United Kingdom Primary Immunodeficiency Network established a registry of cases to collate the nationwide outcomes of COVID-19 in individuals with PID or symptomatic SID and determine risk factors associated with morbidity and mortality from COVID-19 in these patient groups.
RESULTS
A total of 100 patients had been enrolled by July 1, 2020, 60 with PID, 7 with other inborn errors of immunity including autoinflammatory diseases and C1 inhibitor deficiency, and 33 with symptomatic SID. In individuals with PID, 53.3% (32 of 60) were hospitalized, the infection-fatality ratio was 20.0% (12 of 60), the case-fatality ratio was 31.6% (12 of 38), and the inpatient mortality was 37.5% (12 of 32). Individuals with SID had worse outcomes than those with PID; 75.8% (25 of 33) were hospitalized, the infection-fatality ratio was 33.3% (11 of 33), the case-fatality ratio was 39.2% (11 of 28), and inpatient mortality was 44.0% (11 of 25).
CONCLUSIONS
In comparison to the general population, adult patients with PID and symptomatic SID display greater morbidity and mortality from COVID-19. This increased risk must be reflected in public health guidelines to adequately protect vulnerable patients from exposure to the virus
'Attorneys of the poor': Training physicians to tackle health inequalities.
No full textThe stellar gains in life expectancy and health over the past century have been accompanied by an increase in societal and health inequalities. This health gap between the most and least fortunate in our society is widening, driven by complex social determinants of health, as well as healthcare systems themselves. Physicians are not just well-qualified and well-placed to act as advocates for change, but have a moral duty to do so: to stand by silently is to be complicit. Following a workshop on health inequalities and medical training at the Royal College of Physicians Trainees Committee, we sought to examine how health inequalities could be addressed through changes to the medical education system. We discuss the arguments for reform in recruitment to medicine, and changes to undergraduate, postgraduate and continuing medical education in order to equip the profession to deliver meaningful improvements in health inequalities. We propose a population health credential as a mechanism by which specialists can gain additional skills to take on leadership roles addressing health inequalities, allowing them to support colleagues in public health and bring in specialty-specific knowledge and experience
Changes in temperature management and outcome after out-of-hospital cardiac arrest in United Kingdom intensive care units following publication of the targeted temperature management trial.
No full textAIM
To investigate how the publication of the targeted temperature management (TTM) trial in December 2013 affected the trends in temperature management and outcome following admission to UK intensive care units (ICUs) after out-of-hospital cardiac arrest (OHCA).
METHODS
We used a national ICU database of 1,181,405 consecutive admissions to 235 adult ICUs. OHCA admissions mechanically ventilated in the first 24 h in the ICU were divided into a pre-TTM trial cohort of patients admitted before publication of the TTM trial (January 2010-December 2013) and post-TTM cohort of patients admitted after TTM trial publication (January 2014-December 2017). The primary outcome variables were lowest temperature in the first 24 h in ICU and survival to hospital discharge.
RESULTS
The lowest temperature recorded in the first-24 h of admission was significantly higher in the post-TTM cohort (n = 18,106) than in the pre-TTM cohort (n = 12,162) (mean 34.7 (±1.6) versus 33.6 °C (±1.8); absolute difference 1.12 °C (95% CI 1.08-1.16). The post-TTM cohort had a greater prevalence of fever (>38.0 °C) (24.8% vs 14.7%; (odds ratio (OR) 1.91 (95% CI 1.80-2.03); p < 0.001)) and higher unadjusted in-hospital mortality (63.7% vs 61.6%). In a multilevel model, accounting for time trend and including site as a random effect, neither the step change in acute hospital mortality following publication of the TTM trial result (OR 1.04, 95% CI 0.95-1.15; p = 0.37), nor the change in slope (from OR 1.00 per year, 95% CI 0.97-1.04, to 1.04 per year, 95% CI 1.02-1.07; p = 0.059), was statistically significant. Adjusted analyses were limited by the models' dependence on temperature and temperature-related variables.
CONCLUSIONS
The lowest temperature recorded in the first-24 h of admission in OHCA patients was higher in the post-TTM cohort compared with the pre-TTM cohort. There has been an increase in the proportion of patients with fever (>38 °C) in the first 24 h. Although crude mortality was slightly higher in the post-TTM cohort, an analysis accounting for time trend and variation between critical care units, found no significant change associated with the TTM publication